3, 3&#39;-diamino-5, 5&#39;-dicarboxy-hexaiodocarbanilides and derivatives



States Patent i 559,081 s 12 Claims. 01. 260471) *This application is adivision of copending application Ser. No. 285,865, filed .June 6, 1963,now. Patent No. 3,306,927.

' This invention relates to new iodinated organic acids 15 and estersthereof, and to their preparation. More particularly, theinventioncomprises N,N-bis(3-amino-5.- carboxy-2,4,6-triiodophenyl) loweralkanedioic acid amides and 3,3 diamino-5,5' dicarboxy- 2,2,4,4',6,6hexaiodocarbanilides, and derivatives thereof. s

The invention resides in the concept of a composition of matter whereinan N,N-bis(5-carboxy-2,4,6-triiodophenyl)-lower-alkanedioic acid amideis substituted in the 3-positions of both phenyl rings by amino orloweralkanoylamino groups; and to a composition of matter wherein a5,5'-dicarboxy-2,2'4,4'6,6-hexaiodocarbanilide is substituted in the 3-and 3-positions by amino or loweralkanoylamino groups.

The preferred aspects of the invention comprise compounds of thefollowing structural formulas:

COOR

I I I I cook oooR' 40 I I l I (A) From 3-amino-5-nitrobenz0ic acid theinvention are prepared by two OiN NH2 7 III IV 3,409,002 Patented Nov.5, 1968 I (R is NH2) According to the invention, 3-amino-5-nitrobenzoicacid or an ester thereof (III) is caused to react with aloweralaknedioic acid halide, X-COC H CO-X (IV), where X is middlehalogen (chlorine or bromine), to yield anN,N-bis(3-nitro-5-carboxyphenyl)alkanedioic acid amide (V); then thelatter upon catalytic hydrogenation gives anN,N-*bis(3-amino-5-carboxyphenyl)alkanedioic acid amide (VI), which uponiodination gives a compound of Formula I where R is NH The iodinationcan be carried out in acid medium by the addition of an iodinatingagent, e.g., an excess of iodine monochloride or potas' siumiododichloride at room temperature.

In the event R is lower-alkanoylamino conditions are used, e.g., at atemperature about C., the primary product is a compound where R islower-alkanoylamino, only one A ydrogen atom of each amino group beingreplaced by acyl. If higher temperatures are employed, C. or higher,appreciable quantities of the compound where R isbis(loWer-alkanoyl)amino are obtained, both hydrogen atoms of each aminogroup being replaced by acyl.

(B) From 3-amino-5-acylamino-2,4,6-triiodobenzoic acid I (R isaeylamino) The starting materials for this process are known in the artand are prepared as described by Larsen et all, I. l

in French Patent Chem. $06.78, 3210-16 (1956), and 820 M (Brevet Spcialde Mdicament). According to the present invention, a3-amino-5-R-2,4,6-triidobenzoic acid or an ester thereof [wherein R islower-alkanoylamino, lower-alkanoyl(lower-alkyl)amino orbis(loweralkanoyl)amine] (V11) is caused to react with aloweralkanedioic acid halide, X-CO-C H -CO-X (1V), where X is middlehalogen (chlorine or bromine,) to yield a compound of Formula I whereinR' is lower-alkanoylamino, lower-alkanoyl(lower-alkyDamino orbis(loweralkanoyl)a mino. The reaction is preferably carried out byheating the reactants in an inert solvent.

The compounds of Formula 11 can be prepared by process B butsubstituting phosgene (Cl--COC1) for the lower-alkanedioic acid halideThe structures of the compounds of the invention were established by themodes of synthesis, by elementary analysis, and by neutral equivalentdeterminations.

The acid compounds of Formulas I and 11 (R' is hydrogen), in the (formof their water-soluble salts having pharmacologically acceptablecations, e.g., the sodium, calcium or N-methylglucamine salts, exhibitan especially low intravenous toxicity, and when injected into the bloodstream of cats they were found to cause visualization of thegallbladder. The compounds are therefore useful as cholescystographicagents.

' The ester compounds of Formulas I and 11 (R is loweralkyl orphenyl-lower-alkyl) are useful either as intermediates in thepreparation of the acids (R' is hydrogen), or as radiopaque agents forvisualization of body cavities by direct injection therein.

The following examples will further illustrate the invention without thelatter being limited thereby.

Example 1 (a) N,Nbis(3-nitro-5-carboxyphenyl) adipamide [V; n is 4, R isH] .-A solution of 20.5 g. of 3-nitro-5-aminobenzoic acid in 120 ml. oftoluene was refluxed under a water trap to remove slight traces ofwater. Adipyl chloride (9.1 g.) was then added slowly, and the reactionmixture was heated at 100 C. for four hours. The solid product wascollected by filtration, and washed with benzene, dilute hydrochloricacid and water. The solid product was suspended in hot ethanol,collected by filtration, suspended in saturated ammonium chloridesolution, and ammonium hydroxide was added until the mixture was basic.The resulting diammonium salt was collected and recrystallized from 300ml. of water using activated charcoal for decolorizing purposes, thendissolved in 2500 ml. of water and acidified with hydrochloric acid.There was thus obtained 18 g. of N,N'-bis(3-nitro-5-carboxylphenyl)adipamide, M.P. 299.5-301.6 C. (corr.).

By replacing the 3-nitro-S-aminobenzoic acid in the foregoingpreparation by a molar equivalent amount of methyl3-nitro-5-aminobenzoate or benzyl 3-nitro-5- amino-benzoate, there canbe obtained, respectively, N,N'-bis(3-nitro-5-carbomethoxyphenyl)adipamide [V; n is 4, R is CH or N,N-bis(3-nitro-5-carbobenzoxyphenyl)adipamide [V', n is 4, R is CH C H By replacing the adipyl chloride inthe foregoing preparation by a molar equivalent amount of oxalylchloride, malonyl chloride, ride, suberyl chloride or sebacyl chloridethere can be obtained, respectively, N,N'-bis(3-nitro-5-carboxyphenyl)oxamide [V; n is 0, R is H], N,N'-bis(3-nitro-5-carboxyphenyDmalo-namide[V; n is 1, R is H], N,N-bis(3-nitro- 5-carboxyphenyl) glutaramide [V; nis 3, R is H], N,N'- bis(3-nitro-5-carboxyphenyl) {3 methylglutaramide[V; c Hz 1S 0H2, S-carboxyphenyl)suberamide [V; n is 6, RN,N'-bis(3-nitro-5-carboxyphenyl)sebacamide [V', R is H]. V

is H], or n is 8,

glutaryl chloride, fi-methylglutaryl chlo- S-carboxyphenyl)suberamide,or

. adipamide [1; n is 4,

15 N,N'-bis(3-amino-5-carboxyphenyl) adipamide an,

--n is 4, 'R' is-H].A suspension of 79.0 g. of N,N-bis(3-nitro-S-carboxyphenyl)adipamide and 72.5 ml. of hydrazine hydrate in 3liters of water was prepared, and about 10 g. of Raney nickel catalystwas gradually added until frothing ceased. The reaction mixturewasheated for one hour after the nickelhad been added and then acidifiedwith acetic acid. The product was collected by filtration togive 63.4 g.of l I,N-bis(ES-arnino-S-carboxyphenyDadipamide, M.P. 310 C. (dec.)(uncorr.) 'By replacing the N,N-bis(3-nitro-5-carboxyphenyl adipamide inthe foregoing preparation by a r'nolarequivalent amount ofvN,N-bis(3-nitro-S-carbomethoxyphenyl) adipamide, N,N-bis(3 nitro 5carbobenzoxyphenyl) adipamide, N,N-bis(3-nitro 5 carboxyphenyl)oxamide,N,N'-bis('3-nitro-5-carboxyphenyl)malonamide, -N,N bis(3-nitro-5.-carboxyphenyl) glutaramide, N,N -'bis(3-nitro-5-carboxyphenyl)-p-methylglutaramide, N,N-bis(3-nitro-N,N'-bis(3-nitro-5'-c'arboxyphenyl)sebacamide there can be obtained,respectively, N,N-bis(3-amino 5 carbomethoxyphenyl)adipa mide [V1, n is4, R .is CH N,N'-bis(3-amino-5-carbo-- benzoxyphenyl)adipamide [VI; 11is 4, R- is CHZCGHs], N,N-bis(3-amino-5-oarboxyphenyl)oxamide [V1, n is0, R is H], N,N'-bis(3-amino-5-carboxyphenyDmalonamide [V1, rt is 1, Ris H], N,N-bis(3amino-5-carboxyphenyl) glutaramide [V1', 11. is 3, R isH], 'N,Nbis(3-amino-5- carboxyphenyl) {3 methylglutaramide [V1; C H isCH CH(CH )CH R is H], N,N-bis(3-amino-5-carboxyphenyl) suberamide [VI; nis 6, R is H], or N,N'-bis' (3-amino-5-carboxyphenyl) sebacamide [V1, nis 8, R' is H].

(c) N,N' bis(3-amino-5carboxy-2,4,6-triiodophenyl) R is NH R is H] .-Amixture of 26.5 g. of N,N-bis(3-amino-5-carboxyphenyl) adipamide and 192ml. of 2 N aqueous potassium iododichloride solution in 800 ml. ofdistilled water was stirred for sixteen hours at room temperature. Thesolid product was collected by filtration, and the 65.3 g. of crudeN,N-bis(3 amino 5 carboxy-2,4,6-triiodophenyl)adipamide (M1 above 300C.) was converted to the diammonium. salt by treating it with excessammonium hydroxide, and regenerated by the addition of hydrochloricacid. The product was recrystallized from a dimethylformamide-ethanolmixture to giveN,'N'-bis(Ev-amino-5-carboxy-2,4,6-triiodophenyDadipamide, M.P. above300 C. (corn).

The disodium salt of N,Nbis(3-amino-S-carboxy-2,4,6-triiodophenyl)adipamide was prepared by adding 10% aqueous sodiumhydroxide solution to a suspension of the free acid in water until thepH was 7.5-7.7. The disodium salt separated upon addition of isopropylalcohol, and was recrystallized first from water by adding isopropylalcohol and then from absolute methanol by adding ether. The disodiumsalt thus obtained had the M.P. 275.8-276.2 C. (dec.) (corn). Byreplacing the N,N-bis(3-amino-5-carboxyphenyl)- adipamide in theforegoing preparation by a molar equivalent amount ofN,N'-bis(3-amino-S-carbomethbxyphnyl)adiparnide,N,N-bis(3-amino-S-carbobenzoxyphenyl) adipamide, N,Nbis(3-amino-5-carboxyphenyl)oxamide, N,Nbis(3-amino-5-carboxyphenyl)malonamide, N,N'-bis(3-amino-S-carboxyphenyl)glutaramide, N,N bis(3-amino-S-carbOxyphenyl) B methylglutaramide, N,N-bis(3-amino-5-carboxyphenyl)suberamide, or N,N-bis(3-amino-S-carboxyphenyl) sebacamide there can be obtained, respectively,2,4,6-triiodophenyl)adipamide [1; n is 4, R is NH R rs CH N,Nbis(3-amino-S-carbobenzoxy-2,4,6-tniiodophenyl)adipamide [1; n is 4, Ris NH R is CH C H N,N bis(3-amino-S-carboxy-Z,4,6-triiodophenyl)oxarnide[1; n is 0, R is NH R is H], N,N-bis(3-a'mino-5carboxy-Z,4,6-triiodophenyl)malonamide [1; n is l, 'R is z,phenyl)glutaramide [1; n is 3, R is NH R is H], N,N-bis(3-amino-5-carboxy-2,4,6-triiodophenyl) 1S methyl-N,N-.bis(3-amino-5-carbomethoxymethanol. The addition of isopropylalcohol caused separation of "the disodium salt ofN,N'-bis(3-propionylamino carboxy-Z,4,6-triiodophenyl)adipaniide, M.P.265.2270.0 C. (corn).

'N,N bis(3-propionylamino-S-carboxy-Z,4,6-triiodocaused separation salt,M.P. about 230 C. (uncorn).

Example 3 N,N' bis( 3 butyrylamino 5 carboxy2,4,6-triiodophenyl)adipamide [I; n is 4, R is CH CH CH CONH, R is H].Amixture of 28.0 g. ofN,N-bis(3-amino-5-carboxy-2,4,6-triiodophenyl)adipamide, 210 ml. ofbutyric in methyl alcohol. of the dimorpholine N,N bis(3 butyrylamino 5phenyl)adipamide, M.P. about 265 C. (dec.) (corn); disodium salt, M.P.275 C. (dec.) (uncorn) when recrystallized from methanol by the additionof isopropyl alcohol.

By employing a higher temperature, 120150 C., the foregoingprocedure-there can be obtained, N,N'- bis(3 dibutyryl amino 5 carboxy2,4,6 triiodophenyl)adipamide [1; n is 4, R is (CH CH CH CO) N, R is H].

According to the procedures described above in Examples 2 and 3, N,Nbis(3 amino 5 carboxy 2,4,6-

N,N b1s( 3 isobutyrylamino 5 carboxy 2,4,6 triiodophenyD-adipamide [I; nis 4, R is (CH CHCONH, R is H], orN,N-bis(3-formylamino-5-carboxy-2,4,6-tritylamino-5-carboxy-2,4,6-triiodophenyl)-oxamide[I; n is 0, R is CH CONH, R is H], N,N-bis(3-acetylamino-5-carboxy-2,4,6-triiodophenyl)malonamide [1; n is 1, R is CH CONH, R isH], N,N'-bis(3-acetylamino-5-carboxy- 2,4,6 triiodophenyl)glutaramide[1; n is 3, R is CH CONH, R is H], N,N-bis(3-acetylamino-5-carboxy-2,4,6-triiodophenyl)-,B-methylglutaramide [I; C H is CH CH(CH )CH R isCH CONH, R is H], N,N- bis(3 acetylamino 5 carboxy 2,4,6 triiodophenyl)suberamide [I; n is 6, R is CH CONH, R is H] or N,N- bis(3 acetylamino 5carboxy 2,4,6 triiodophenyl) sebacamide [I; n is 8, R is CH CONH, R isH].

Example 4 (a) 3,3-dinitro-5,5-dicarboxycarbanilide-A solution of 53.2 g.of 3-amino-5-nitrobenzoic acid in 750 ml. of chlorobenzene was prepared,and 50 ml. of 20% phoswas added. The reaction mixture at C. for fivehours. The

hot Water. There was thus obtained 3,3-dinitro-5,5-dicarboxycarbanilide,M.P. 303-307 C. ('dec.) (uncorr.).

By replacing the 3-amino-5-nitrobenz0ic acid in the foregoingpreparation by a molar equivalent amount of methyl3-amino-5-nitrobenzoate or benzyl 3-amino-5- nitrobenzoate there can beobtained, respectively, 3,3- dinitro-S,5-dicarbomethoxycarbanilide or3,3-dinitro- 5,5-dicarbobenzoxycarbanilide.

(b) 3,3-diamino-5,5-dicarboxycarbanilide was prepared from 70.0 g. of3,3-dinitro-5,5-dicarboxycarbanilide, and 78 ml. of 100% hydrazinehydrate in 2000 ml. of water in the presence of Raney nickel catalystaccording to the procedure described above in Example 1, part (b). Theproduct was purified by converting it to the disodium salt with anexcess of 10% sodium hydroxide was collected by filtration to give3,3'-diamino-5,5-dicarboxycarbanilide in the form of itsmonohydrochlon'de salt, M.P. above 300 C.

By replacing the 3,3-dinitro-5,5-dicarboxycarbanilide by a molarequivalent amount of 3,3-dinitro-5,5-dicarbomethoxycarbanilide or3,3-dinitro-5,5-dicarbobenzoxycarbanilide there can be obtained,respectively, 3,3- diamino-5,5-dicarbomethoxycarbanilide or 3,3-diamino-5,5-dicarbobenzoxycarbanilide.

(c) 3,3 diamino 5,5 dicarboxy 2,2,4,4,6,6- hexaiodocarbanilide [II; R isNH R is H] .A mixture of 47.6 g. of3,3-diamin0-5,5-dicarboxycarbanilide, 390

by repeated suspension in boiling ethanol. There was thus I obtained3,3'- diamino-5,5'-dicarboxy-2,2',4,4',6,6-hexaiodocarbanilide, M.P.above 300 C. (corn).

By replacing the 3,3-diamino-5,5-dicarboxycarbanilheated on a steammixture was cooled, and the solid ide in the foregoing preparation by amolar equivalent amount of 3,3-diamino5,5-dicarbomethoxycarbanilide or3,3-diamino-5,5-dicarbobenzoxycarbanilide there can Example 3,3diacetylamino 5,5 dicarboxy 2,2,4,4,6,6- hexaiodocarbanilide [11; R isCH CONH, R is H].A mixture of 7.2 g. of3,3-diamino-5,5-dicarboxy-2,2,4,4, 6,6'-hexaiodocarbanilide, 35 ml. ofacetic anhydride and 2 drops of concentrated sulfuric acid was stirredand bath for three hours. The reaction product was collected byfiltration and purified by suspending it in 200 ml. of boiling methanol.The product was finally washed with acetone and ether and dried to give7.0 g. of 3,3'-diacetylamino 5,5 dicarboxy 2,2,4,4,6,6'hexaiodocarbanilide, M.P. above 300 C. (corn).

By replacing the 3,3-diamino-5,5-dicarboxy-2,2,4,4,6,6hexaiodocarbanilide in the foregoing preparation by a molarequivalent amount of3,3'-diamino-5,5-dicarbomethoxy-2,2,4,4,6,6'-hexaiodocarbanilide or3,3-diamino 5,5 dicarbobenzoxy 2,2,4,4,6,6 hexaiodocarbanilide there canbe obtained, respectively, 3,3-diacetylamino 5,5 dicarbomethoxy2,2,4,4,6,6 hexaiodocarbanilide [11; R is CH CONH, R is CH or3,3-diacetylamino 5,5 dicarbobenzoxy 2,2,4,4,6,6' hexaiodocarbanilide[11; R is CH CONH, R is CH Example 6 3,3 dipropionylamino 5,5 dicarboxy2,2,4,4,6, -hexaiodocarbanilide [11; 1-1] was prepared from 10.8 g. of3,3-diamino-5,5-dicarboxy-2,2,4,4',6,6'-hexaiodocarbanilide, 50 ml. ofpropionic anhydride and drops of concentrated sulfuric acid. Thereaction mixture was heated on a steam bath for seventeen hours, and theproduct Was purified through the diammonium salt to give 7.2 g. of3,3-dipropiony1- amino 5,5 dicarboxy 2,2,4,4,6,6' hexaiodocarbanilide,M.P. above 300 C. (uncorr.).

3,3 dipropionylamino 5,5 dicarboxy 2,2,4,4,6, '-hexaiodocarbanilide (7.1g.) and 2.34 g. of N-methylglucarnine were ground together in a mortarand then suspended in 300 ml. of hot methanol. Distilled water (150 ml.)Was added and the solution was filtered and concentrated to dryness. Theresidue was suspended in boiling ethanol and the solid product collectedby filtration. There was thus obtained 8.6 g. of 3,3-dipropionylamino5,5 dicarboxy 2,2',4,4,6,6 hexaiodocarbanilide in the form of itsdi-N-methylglucamine salt, M.P. 187.2188.0 C. (dec.) (corn).

Example 7 3,3 dibutyrylamino 5,5 dicarboxy 2,2,4,4',6,6-hexaiodocarbanilide [11; R is CH C1-1 CH CONH, R is H] was prepared from10.8 g. of 3,3-diamino-5,S-dicarboxy 2,2,4,4,6,6'-hexaiodocarbanilide,50 ml. of n-butyric anhydride and 10 drops of concentrated sulfuric acidby the procedure described above in Examples 5 and 6. There was thusobtained 9.3 g. of 3,3-dibutyrylamino 5,5 dicarboxy 2,2,4,4,6,6'hexaiodocarbanilide, M.P. about 260 C. (dec.) (uncorr.);di-N-methylglucamine salt, M.P. 200.4-201" C. (dec.) (corn).

Example 8 3,3-divalerylamino-5,5-dicarboxy-2,2,4,4,6,6'hexaiodocarbanilide [11; R is CH (CH CONH, R is H] was prepared from14.2 g. of 3,3-diamino-5,5-dicarboxy-2,2',4,4,6,6-hexaiodocarbanilide,53 ml. of n-valeric anhydride and 10 drops of concentrated sulfuric acidaccording to the procedures described above in Examples 5 and 6. Therewas thus obtained 9.4 g. of 3,3-divaleryl- R is CH C1-1 CONH, R is 8amino-5,5-dicarboxy-2,2,4,4,6,6 hexaiodocarbanilide, M.P. 245-247 C.(dec.) (uncorn); di-N-methylglucamine salt, M.P. 188-190 C. (dec.)(uncorr.).

According to the foregoing procedures 3,3-diamino-5,5'-dicarboxy-2,2,4,4,6,6'-hexaiodocarbanilide can be caused to reactwith n-caproic anhydride, isova leric anhydride, or an aceticanhydride-formic acid mixture to give, respectively,3,3-dicaproylamino-5,5-dicarboxy-2, 2',4,4,6,6-hexaiodocarbanilide [11;R is R is H], 3,3-diisovalerylamino-5,5-dicarboxy-2,2',4,4,6,6-hexaiodocarbanilide [11; R is (CH CHCONH, R is H], or3,3-diformylamino-5,5-dicarboxy-2,2,4,4,6,6'- hexaiodocarbanilide [11; Ris HCONH, R is 1'1].

Example 9 3,3-bis(dipropionylarnino) 5,5 dicarboxy-2,2'4,4 ,6,6-hexaiodocarbanilide [11; R is (CH CH CO) N, R is H] .A mixture of 13.5g. of 3,3-diamino-5,5-dicarboxy- 2,2 ,4,4,6,6-hexaiodocarbanilide, 124ml. of propionic anhydride and 4 drops of concentrated sulfuric acid washeated at 120-130 C. for three hours. The reaction mixture was cooled,and the solid product was collected and purified through its ammoniumsalt and by suspension in boiling methanol. There was thus obtained3,3'-bis(dipropionylamino)-5,5-dicarboxy2,2',4,4,6,6-hexaiodocarbanilide, M.P. above 300 C. (corn).

Example 10 (a) Benzyl 3-acetylamino-5-amino-2,4,6-triiodobenzoate.-Amixture of 22.8 g. of 3-acetylamino-5-amino-2,4, 6-triiodobenzoic acid,6.5 g. (5.9 ml.) of benzyl chloride and 2.3 g. of anhydrous sodiumcarbonate in ml. of dimethyltormamide was heated on a steam bath fortwenty hours. The reaction mixture was poured into 600 ml. of coldwater, and the solid product was collected by filtration, washed withcold water and dried to give 23.5 g. of benzyl3-acetylamino-5-amino-2,4,6-triiodobenzoate, M.P. 198200 C. (uncorr.)when recrystallized from 100 ml. of chlorobenzene.

(b) N,N-bis(3-acetylamino 5-carbobenzoxy'-2,4,6-tri-'iodophenyl)adipamide [1, n is 4, R is CH CONH, R is CH C H ].Adipic acidchloride (1.5 g.) was added dropwise to a solution of 16.1 g. of benzyl3-acetylamino- 5-amino-2,4,6-triiodobenzoate in 50 ml. of chlorobenzeneat C. The reaction mixture was stirred and heated for two hours, and thesolid product was collected by filtration, triturated with ether,repeatedly suspended in boiling acetone and collected to give 8.6 g. ofN,N-his(3- acetylamino-S-carbobenzoxy 2,4,6-triiodophenyl) adipamide,M.P. 268-269" C. (dec.) (uncorn).

(c) N,N-bis(3-acetylaimino-5 carboxy 2,4,6-triiodophenyl)adipamide [1;\n is 4, R is CH CONH, R is H].-A mixture of 11.26 g. ofN,N-bis(3-acetylamino- 5-canbobenzoxy-2,4,6-triiodophenyl)adipamide and100 ml. of 30% hydrogen bromide in acetic acid was allowed to stand atroom temperature for several days. The reaction mixture was poured intoice water, the mixture allowed to warm to room temperature, and thesolid product was collected by filtration and washed with cold water.The product was suspended in water, a slight excess of ammoniumhydroxide was added and the solution of diammonium salt extracted withether to remove benzyl bromide. The aqueous solution was decolorizedwith activated charcoal, filtered and made acid with hydrochloric acid.The free acid, N,N'-bis(3-acetylamino-5-carboxy-2,4,6-triiodophenyl)adipamide, was collected by filtration.

A solution of 5.7 g. ofN,N-bis(3-acetylamino-5-carboxy-2,4,6-triiodophenyl)adipamide in 100 ml.of anhydrous methanol was added to a solution of 1.95 g. of N-methylglucamine in natant liquid was decanted from the gum which hadseparated, and the gum was 100 ml. of methanol. The super-.

triturated with acetone to give 5.1

9 g. of N,N-bis(3 acetylamino 5 -carboxy-2,4,6-triiodophenyl)adipamidein the form of its di-N-methylglucamine salt, M.P. l85.2 C. (corn).

To a suspension of 33.23 g. of N,N-bis(3-acetylamino-S-carboxy-2,4,6-triiodophenyl)adipamide in 37 ml.

and the solid product was separated N,N'-bis(3-acetylamino-5-carboxy2,4,6-triiodophenyl)- adipamide in the form of its disodium salt, M.P.264.2- 270.0' C. (dec.) (corn).

Example 11 3,3-diacetylamino 5,5 dicarbobenzoxy-2,2,4,4,6,6'-hexaiodocarbanilide [II; R is CH CONH, R is CH C H ].To a boilingsolution of 33.0 g. of benzyl3-acetylamino-5-amino-2,4,6-tr1iodobenzoate in 125 ml. of

collected and washed with hot chlorobenzene. To the filtrate was added8.0 ml. of 20% phosgene in toluene and the mixture was refluxed forninety minutes. The

the solid prodto give 3,3-diacetylamino-5,5'-dicarbobenzoxy-2,2,4,4,6,6'hexaiodocarbanilide, M.P. 263.2 C. (dec.) (corn).

3,3-diacetylamino-S,S-dicarbobenzoxy 2,2,4,4,6,6'- hexaiodocarbanilidecan phosgene CH CO(CH )N R is H].

I claim: 1. A compound of the formula COOR $0011 R NH-C ONH wherein R isa member of the group consisting of amino,

10 lower-alkanoyl (lower-alkyl) amino is a member of lower-alkyl andlower-alkanoylamino, and bis(lower-alkanoyDamino; and R the groupconsisting of hydrogen, phenyl-lower-alkyl.

A compound according to claim 1 lower-alkanoylamino and R is hydrogen.

3. 3,3-diacetylamino-5,5'-dicarb0benzoxy-2,2,4,4,6,6-hexaiodocarbanilide, according to claim 1 wherein R is acetylamino and Ris benzyl.

4. 3,3-diamino-5,5-dicarboxy-2,2,4,4',6,6' hexaiodocanbanilide,according to claim 1 wherein R is amino and R is hydrogen.

5. 3,3 diace tylatmino 5,5 dicarboxy 2,2',4,4,6,6'- hexaiodocarbanilide,according to claim 2 wherein R is acetylamino.

6. 3,3-dipropionylamino 5,5 dicarboxy-2,2',4,4,6,6- hexaiodocarbanilide,according to claim 2 wherein R is propionylamino.

7. 3,3'-bis(dipropionylamino)-5,5-dicarboxy 2,2,4,4',6,6,-hexaiodocarbanilide, according to claim 1 wherein isdipropionylamino and R is hydrogen.

8. 3,3'-dibutyrylamino-5,5-dicanboxy-2,2',4,4',6,6'-hexaiodocarbanilide,according to claim 2 wherein R is butyrylarnino.

9. A compound of the formula of the group consisting ofphenyl-lower-alkyl.

according to wherein R is wherein R is a member hydrogen, lower-alkyland 10. 3,3 dinitro-S,5-dicarboxycarbanilide, claim 9 wherein R ishydrogen.

11. A compound of the formula COOR 000R wherein R" is a member of thegroup consisting of hydrogen, lower-alkyl and phenyl-lower-alkyl.

12. 3,3-diamino-S,5'-dicanboxycarbanilide, according to claim 11 whereinR is hydrogen.

References Cited UNITED STATES PATENTS 3,128,301 4/1964 Larsen et al.

LORRAINE A. WEINBERGER, Primary Examiner. L. ARNOLD THAXTON, AssistantExaminer.

1. A COMPOUND OF THE FORMULA